New data demonstrate that a regimen of venetoclax in combination with cytarabine and azacitidine indicate a safe, new treatment choice for patients with relapsed/refractory (R/R) acute myeloid leukemia (AML), especially in European LeukemiaNet intermediate/adverse groups, as well as in those patients with advanced ages. 

Lead author Liangshun You, MD, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China reported this data at the 2023 American Society of Clinical Oncology (ASCO) annual meeting.

This open-label, single-arm, phase 2 trial included 30 patients aged 18 to 70 years who had a confirmed diagnosis of relapsed/refractory AML. A stepwise ramp-up of venetoclax dosing was required to achieve the target dose of 400 mg, beginning with 100mg on day 1, 200mg on day 2, and 400 mg on days 3 through 9. Cytarabine (10mg/m2) was administered by subcutaneous injection twice daily from day 1 to day 10, and azacitidine (75mg/m2) was administered by intravenous injection once daily from day 1 to day 7.

The measured primary efficacy endpoints were composite complete response including complete response and complete remission with incomplete count recovery, partial response, and morphologic leukemia-free state per the International Working Group for AML. Secondary endpoints were overall survival (OS) and duration of response.

Results demonstrated that the composite complete response rate among all eligible patients was achieved in 62.1% (18/29), which included complete response in 34.5% and complete remission with incomplete count recovery in 27.6% patients, with 13.8% of patients obtaining partial response.

Composite complete response rates were noted to be preserved across subgroups with 59.1% (13/22) in European LeukemiaNet intermediate/adverse group, 62.5% (5/8) in patients aged  ≥65 years, and 50% (7/14) in patients whose baseline bone marrow count was ≥30%.

Additionally, the composite complete response rate in patients diagnosed with subtypes M4/5 reached 72.7% (8/11). At a measured median follow-up of 6.95 months, the median OS and median duration of response were not yet reached. The projected 12-month OS was 86%, while the measured 12-month duration of response was 62.6%. This treatment regimen had similar efficacy in patients younger than 65 years compared with those older than 65 years.

No tumor lysis syndrome events were observed throughout the trial, and no treatment-related deaths occurred.

“[This] regimen represents a feasible and safe new choice for R/R AML patients, especially with satisfactory effect in ELN intermediate/adverse group and in those with advanced ages,” You and colleagues concluded. 

Source:

You L, Liu Y, Mai W, et al. Efficacy and safety of venetoclax in combination with cytarabine and azacitidine (VAA) in relapsed/refractory acute myeloid leukemia: An open-label, single-arm, phase II study. Presented at the ASCO Annual Meeting; June 2-6, 2023; Chicago, Illinois. Abstract 7025.